Cyclosporin A (CsA) is a cyclic undecapeptide of fungal origin and has potent immunosuppressant activity. It is widespreadly used in clinical transplantation for prevention of kidney, liver, pancreas and heart allograft rejection and for treating bone marrow recipients with acute graft v. host disease. It has also been suggested for use in the treatment of autoimmune diseases, malaria and schistosomiasis. Although CsA is not myelosuppressive, clinically important complications associated with CsA therapy include nephrotoxicity, hepatotoxicity and CNS disturbances.
CsA appears to act on the immune system by inhibiting the initial steps of interleukin-1 and antigen coactivation of T lymphocytes. It also blocks the production of interleukin-2 required for the differentation and proliferation of B cells and precursor cytolytic T cells. CsA also inhibits production of gamma interferon and lymphokines that mediate the delayed-type hypersensitivity and reactions and activate macrophages.
Merker et al, Cyclosporin Binding Components in BW5147 Lymphoblast and Normal Lymphoid Tissue, Transplantation Proceedings, Vol. XV, No. 4, Supplement 1, p. 2265 et seq. (December, 1983), reports the discovery of a high affinity binding component for CsA in the cytosol of normal T cells as well as a malignant cell line and the partial purification of the binding component from calf thymus as well as the malignant cell line. Purification was by molecular weight exclusion columns, isoelectric focusing and (NH.sub.4).sub.2 SO.sub.4 precipitation to about 10% purity. The CsA-cytosol complex was indicated to have a molecular weight of 15,000-20,000.
It is the object of this invention to provide a new homogeneous cytosolic binding protein, cyclophilin, and affinity matrices containing cyclophilin and further to provide methods of using the cyclophilin as an affinity reagent in diagnostic and preparatory procedures.